DNA methylation age of human tissues and cell types

Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA

Human Genetics, Gonda Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-7088, USA

Genome Biology 2013, 14:R115
doi:10.1186/gb-2013-14-10-r115

Published: 21 October 2013

Abstract

Background

It is not yet known whether DNA methylation levels can be used to accurately predict
age across a broad spectrum of human tissues and cell types, nor whether the resulting
age prediction is a biologically meaningful measure.

Results

I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation
age of most tissues and cell types. The predictor, which is freely available, was
developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing
51 healthy tissues and cell types. I found that DNA methylation age has the following
properties: first, it is close to zero for embryonic and induced pluripotent stem
cells; second, it correlates with cell passage number; third, it gives rise to a highly
heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee
tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the
considered 20 cancer types exhibit significant age acceleration, with an average of
36 years. Low age-acceleration of cancer tissue is associated with a high number of
somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation
age in breast cancer. Finally, I characterize the 353 CpG sites that together form
an aging clock in terms of chromatin states and tissue variance.

Conclusions

I propose that DNA methylation age measures the cumulative effect of an epigenetic
maintenance system. This novel epigenetic clock can be used to address a host of questions
in developmental biology, cancer and aging research.